Abstract ThisproposalwillleadtoaBreakthroughsub?cellular3Dchemicalcompositionresearchplatformforlive cells,basedonthenewinventionofsub?micronconfocalphotothermalIRmicro?spectroscopy(CPIR). Label?freesub?micronchemicalimagingandspectroscopyhaslongbeensoughtforvisualizationof biomoleculesandmaterialsincomplexlivingsystems.Manydiseasesfirstmanifestthemselvesatthe cellular,orsubcellularlevel.IRmicro?spectroscopyisapowerfultechniquebutitsuseinlifesciencesin generalandcellularanalysisinparticularhasbeenlimitedduetothefollowing2keylimitations: a)Spatialresolutionlimitedbydiffractionto~10m. b)Inabilityforin?vivoimagingduetostrongIRabsorptionbywater. Thisproposaleliminatesbothoftheabovelimitationsandisbasedonarecentlypublishedpatent? pendingbreakthroughbythePI,Prof.Ji?XinChengofBostonUniversityandislicensedexclusivelyby AnasysInstrumentsforcommercialization.Prof.Chengisoneoftheworld'sleadingvibrational spectroscopyresearchersandistheco?inventoroftheCARS(CoherentAnti?StokesRamanScattering) microscope,whichisamajorinnovationinthefieldofRamanSpectroscopy.Anasyspioneeredthefield ofAFM(Atomicforcemicroscope)basedphotothermalnanoscaleIRSpectroscopywhereanAFM probedetectsthephotothermalsignalinducedbyIRabsorption. Thegoalofthisproposalistocreateahighspeedconfocalopticalmicroscopyplatformcapableof300 nmIRSpectroscopyinfluid.Thisplatformcanbeusedinsub?cellularchemicalcompositionresearchof livecellswhichhasmanyapplicationsinthelifesciences. TheproposedCPIRplatformishighlyinnovativebecauseitwouldenablereal?timeimagingoflipid metabolitesinsinglelivetumorcellsbasedonfingerprintIRbands.Comparedtothewidelystudied geneticaspectofcancerandthewell?knownWarburgeffect,appreciationoftheroleoflipidsincancer developmentisstillemerging.Aberrantexpressionsoflipogenicgeneshavebeenfoundinbrain, mammary,prostateandmanyothercancer.Evenwiththesediscoveries,lipidmetabolismhasnotbeen usedasaprognosticfactorforcanceraggressivenessduetolackofdifferentialdetectionand quantitationtechnology.Ourproposalaimstofillthisgapbyquantifyingtheamountandcompositionof lipiddroplets,animportantaspectoflipogenesisintumorcells.Thoughwefocusonlipidmetabolites here,ourspectroscopicimagingplatformisgenerallyapplicabletomonitortheintracellulardynamicsof othermetabolites,anti?cancerdrugs,andnutritionmoleculessuchasfattyacidsandaminoacids,thus havingafar?reachingimpactoncancerresearch.